Protection of Human Subjects. Policies and Procedures Federal by hijuney5


									31738                                                         NOTICES

    DEPARTMENT OF HEALTH,                    the improvement of the health of the Na-       (An abortus having the capacity to sus-
    EDUCATION, AND WELFARE                   tion’s people through research, develop-       tain heart beat and respiration is in fact
                                             ment, and demonstration activities which       a premature infant, and all regulations
         National Institutes of Health       at times involve human subjects. Thus,         governing research on children apply.)
   PROTECTION OF HUMAN SUBJECTS              policies and procedures are required for          b. The fetus in utero. No research
                                             the protection of subjects on whose par-       involving pregnant women shall be con-
           Policies and Procedures           ticipation these activities depend.            ducted unless:
   In the FEDERAL REGISTER of October 9,        Informed consent is the keystone of            1. Primary Review Groups assure that
1973 (38 FR 27882 et seq.), the Secre- the protection of human subjects in-                 the activity is not likely to harm the
tary of Health, Education, and Welfare volved in research, development, and                 fetus;
issued a notice of proposed rulemaking demonstration activities. Certain cate-                 2. the agency Ethical Review Board
concerning the protection of human sub- gories of persons have limited capacity             has reviewed the activity;
jects and mentioned that DHEW through to concent to their involvement in such                  3. a Protection Committee is operat-
the National Institutes of Health, had activities. Therefore, as a supplement to            ing in a manner approved by the agency;
appointed a special study group to re- DHEW policies, special protections are               and
view and recommend policies and special proposed for children, prisoners, and the              4. the consent of both prospective
procedures for the protection of chil- mentally infirm who are to be involved               legal parents has been obtained, when
dren, prisoners, and the institutionalized in research, development, and demon-             reasonably possible.
mentally infirm in research, develop- stration activities.                                     C. Products of in vitro fertilization. No
ment, and demonstration activities. The         Agency “Ethical Review Boards” are to       research     involving   implantation      of
report of this study group has been com- be established to provide rigorous review          human ova which have been fertilized
pleted in draft form and reviewed by the of the ethical issues in research, develop-        in vitro shall be approved until the
Director, NIH.                               ment, and demonstration activities in-         safety of the technique has been demon-
   There may well be elements in the volving human subjects, in order to                    strated as far as possible in sub-human
recommendations which will provoke make judgments regarding societal ac-                    primates, and the responsibilities of the
debate and controversy. We recognize ceptability in relation to scientific value.           donor and recipient “parents” and of
that public consideration and comment “Protection Committees” are to be estab-              research institutions and personnel have
are vital to the development of our final lished by the applicant to provide “sup-          been established. Therefore, no such re-
recommendations to the Secretary and plementary judgment” concerning the                    search may be conducted without review
are inviting such comment now even reasonableness and validity of the con-                  of the Ethical Review Board and of a
though the materials are still pending sent given by, or on behalf of, subjects.            Protection Committee.
final review and completion. The product The intent of this policy is that institu-            3. Prisoners. Research, development,
of our effort after considering public tions which apply for DHEW funds or                  and demonstration activities involving
comment will be transmitted to the As- submit research in fulfillment of DHEW               human subjects often require the partic-
sistant Secretary for Health, HEW to regulations, must be in compliance with                ipation of normal volunteers. Prisoners
recommend to the Secretary, HEW that these special protections, whether or not              may be especially suitable subjects for
it appear again in the FEDERAL REGISTER particular research, development, or dem-           such studies, although there are prob-
as proposed rulemaking for further pub- onstration activities are Federally activ-          lems concerning the voluntariness of the
lic comment. Such a procedure is con- ities.                                                consent of normal volunteers who are
sistent with long established DHEW pol-         1. Children. If the health of children is   confined in institutions. Certain pro-
icy for permitting extensive public op- to be improved, research activities in-             tections are required to compensate for
portunity to affect the promulgation of volving their participation is often essen-         the diminished autonomy of prisoners in
DHEW regulations.                            tial. Limitation of their capacity to give     giving voluntary consent. Research, de-
                                             informed consent, however, requires that       velopment, and demonstration activities
   It must be clearly understood by the certain protections be provided to assure
reader that the material that follows is that scientific importance is weighed              involving prisoners must:
not proposed rulemaking in the technical against other social values in determining            a. Include the applicant’s proposal for
sense, and is not presented as Depart- acceptable risk to children. Therefore,              use of a Protection Committee which is
mental, Public Health Service, or NIH research, development, and demonstra-                 appropriate to the nature of the activity;
policy. Rather it is a draft working docu- tion activities which involve risk to chil-         b. Be reviewed and approved by an
ment on which early public comment dren who participate must:                               Organizational Review Committee which
and participation is invited.                                                               may already exist in compliance with
                                                a. Include a mechanism for obtaining        present DHEW policy or which must be
   Please address any comments on these the consent of children who are 7 years
                                                                                            appointed in a manner approved by the
draft policies and procedures to the Di- of age or older;
rector, National Institutes of Health, 9000                                                 appropriate DHEW agency;
                                                b. Include the applicant’s proposal for        c. Be reviewed by the agency Primary
Rockville Pike, Bethesda,           Maryland use of a Protection Committee which is
20014. All comments should be received appropriate to the nature of the activity;           Review Committee; and
by January 4, 1974.                                                                            d. Be conducted in an institution
                                                c. Be reviewed and approved, in con-        which is accredited by the Secretary of
   Additional copies of this notice are formity with present DHEW policy, by                Health, Education, and Welfare.
available from the Chief, Institutional an Organizational Review Committee;                    4. The mentally infirm. Insofar as the
Relations Branch, Division of Research and                                                  institutionalized mentally infirm might
Grants, National Institutes of Health.          d. Be reviewed by the appropriate           lack either the competency or the au-
9000 Rockville Pike, Bethesda, Maryland agency Primary Review Committee, the                tonomy (or both) to give informed con-
20014.                                       Ethical Review Board, and the appro-           sent, their participation in research re-
                                             priate secondary review group.                 quires additional protection:
    Dated: November 6, 1973.                    2. Special categories. —a. The Abortus.        a. Research, development and demon-
                     ROBERT S. STONE,        No research, development, or demonstra-        stration activities involving the mentally
                                Director,    tion activity involving the non-viable         infirm will be limited to investigations
           National Institutes of Health.    abortus shall be conducted which:              concerning (1) diagnosis, etiology, pre-
                                                1. Will prolong heart beat and respira-     vention, or treatment of the disability
RESEARCH, DEVELOPMENT, AND DEMONSTRA- tion artificially solely for the purpose of
    TION ACTIVITIES:     LIMITATIONS OF IN- research;                                       from which they suffer, or (2) aspects of
    FORMED CONSENT                                                                          institutional life, per se, or (3) infor-
                                                2. Will of itself terminate heart beat      mation which can be obtained only from
       SPECIAL POLICY CONSIDERATIONS         and respiration;                               such subjects.
                   Summary                      3. Has not been reviewed by the agency         All research, development and demon-
                                             Ethical Review Board; and                      stration activities involving such per-
                         NOVEMBER 5, 1973.
                                                4. Has not been consented to by the         sons must :
   The mission of the Department of pregnant woman with participation of a                     1. Include the applicant’s assurance
Health, Education, and Welfare includes Protection Committee.                               that the study can be accomplished only

                                   FEDERAL REGISTER, VOL. 38, NO. 221—FRIDAY, NOVEMBER 16, 1973
                                                                 NOTICES                                                           31739
with the participation of the mentally           information provided and to formulate            3. Studies which are related to a pa-
infirm;                                          the judgments on which valid consent          tient’s disease but from which he or she
   2. Include the applicant’s proposal           must depend. In addition, current poli-       will not necessarily receive any direct
for use of a Protection Committee which          ties for clinical research afford such sub-   benefit.
is appropriate to the activity; and              jects inadequate protection. Nevertheless,       4. Investigative, non-therapeutic re-
   3. Be reviewed and approved by an             to proscribe research on all such subjects,   search in which there is no intent or ex-
Organizational Review Committee, in              simply because existing protections are       pectation of treating an illness from
conformity with present DHEW policy.             inadequate, would be to deny them po-         which the patient is suffering, or in
            TABLE OF CONTENTS                    tential benefits, and is, therefore, in-      which the subject is a “normal control”
                                                 equitable. Knowledge of some diseases         who is not suffering from an illness but
Introduction.                                    and therapies can be obtained only from       who volunteers to participate for the po-
    I. Definitions.
   II. General policy considerations.
                                                 those subjects (such as children) who         tential benefit of others.
 III. Children.                                  suffer from the disease or who will be           It is important to emphasize that
       A. Policy considerations.                 receiving the therapy. Their participa-       “non-therapeutic” is not to be under-
       B. Agency Ethical Review Board: Eth-      tion in research is necessary to progress     stood as meaning “harmful.” Under-
            ical review of projects.             in those fields of medicine. When such        standing of normal processes is essen-
       C. Protection Committee: Protection of    subjects participate in research, they        tial; it is the prerequisite, in many in-
            individual subjects.                 need more protection than is provided         stances, to recognition of those devia-
       D. Special provisions.                    by present policy.
       E. The fetus.
                                                                                               tions from normal which define disease.
  IV. Special categories.                           There are other individuals who might      Important knowledge can be gained
       A. The abortus.                           be able to comprehend the nature of the       through such studies of normal proc-
       B. The products of in vitro fertiliza-    research, but who are involuntarily con-      esses. Although such research might not
            tion.                                fined in institutions. Insofar as incar-      in any way benefit the subjects from
   V. Prisoners.                                 ceration might diminish their freedom         whom the data are obtained, neither
       A. Policy considerations.                 of choice, and thus limit the degree to       does it necessarily harm them.
       B. Organizational Review Committee.       which informed consent can be freely             Patients participating in studies iden-
       C. Protection Committee.
       D. Payment to prisoners.                  given, they too need additional protec-       tified in paragraph B–1, above, are not
       E. Accreditation.                         tion. Current policies do not recognize       considered to be at special risk by virtue
       F. Special provisions.                    the limitations on voluntariness of con-      of participating in research activities,
  VI. The mentally infirm.                       sent which may emanate from incar-            and this policy statement offers no spe-
       A. Policy considerations.                 ceration.                                     cial protection to them. When patients
       B. Ethical review of projects and pro-       This addition to existing policy is of-    or subjects are involved in procedures
            tection of subjects.                 fered as a means of providing adequate        identified in paragraphs B2, B3, and B4,
 VII. General provisions.                        protection to subjects who, for one rea-
       A. Referrals to the Ethical Review                                                      they are considered to be “at risk,” and
            Board.                               son or another, have a limited ability to     the special policy and procedures set
       B. Procedures requiring special consid-   give truly informed and fully autono-         forth in this document pertain. Excluded
            eration.                             mous consent to participate in research.      from this definition are studies in which
       C. Research conducted in foreign coun-    The aim is to set standards which are         the risk is negligible, such as research re-
            tries.                               both comprehensive and equitable, in          quiring only, for example, the recording
       D. Research submitted pursuant to         order to provide protection and, to the       of height and weight, collecting excreta,
            DHEW regulatory requirements.        extent consistent with such protection,       or analysing hair, deciduous teeth, or nail
       E. Clinical research not funded by        maintain an environment in which clin-
            DHEW.                                                                              clippings. Some studies which appear to
       F. Confidentiality of information and     ical research may continue to thrive.         involve negligible physical risk might,
            records.                                1. Definitions. For purposes of this       however, have psychological, sociological
VIII. Draft regulations.                         policy:                                       or legal implications which are signifi-
                                                    A. Subject at risk means any individ-      cant. In that event, the subjects are in
               INTRODUCTION                      ual who might be exposed to the possi-        fact “at risk,’’ and appropriate proce-
   The mission of the Department of              bility of harm (physical, psychological,      dures described in this document shall
Health, Education, and Welfare includes          sociological, or other) as a consequence      be applied.
the improvement of the health of the             of participation as a subject in any re-
                                                 search, development or demonstration             C. Children are individuals who have
Nation’s people through biomedical re-                                                         not attained the legal age of consent to
search. This mission requires the estab-         activity (hereinafter called “activity”)
                                                                                               participate in research as determined
lishment of policy and procedures for the        which goes beyond the application of es-      under the applicable law of the jurisdic-
protection of subjects on whose partici-         tablished and accepted methods neces-         tion in which the proposed research is to
pation that research depends. In DHEW            sary to meet his needs.                       be conducted.
policy, as well as in ethical codes per-            B. Clinical research means an inves-          D. Pregnancy encompasses the period
taining to research in human subjects,           tigation involving the biological, behav-     of time from implantation until delivery.
the keystone of protection is informed           ioral, or psychological study of a per-       All women during the child bearing years
consent.                                         son, his body or his surroundings. This       should be considered at risk of preg-
   An uncoerced person of adult years            includes but is not limited to any medi-      nancy; hence, prudence requires defini-
and sound mind may consent to the ap-            cal or surgical procedure, any withdraw-      tive exclusion of pregnancy when women
plication of standard medical procedures         al or removal of body tissue or fluid, any    in this period of life are subjects for ex-
in the case of illness, and when fully and       administration of a chemical substance,       perimentation which might affect the
properly informed, may legally and               any deviation from normal diet or daily       fetus.
ethically consent to accept the risks of         regimen, and any manipulation or ob-             E. Fetus means the product of concep-
participating in research activities. Par-       seravtion of bodily processes, behavior       tion from the time of implantation to
ents and legal guardians have authority          or environment. Clinical research com-        the time of delivery from the uterus.
to consent on behalf of their child or           prises four categories of activity:
                                                                                                  F. Abortus means a fetus when it is
ward to established therapeutic proce-              1. Studies which conform to estab-         expelled whole, whether spontaneously
dures when the child is suffering from an        lished and accepted medical practice          or as a result of medical or surgical inter-
illness, even though the treatment might         with respect to diagnosis or treatment of     vention undertaken with the intention
involve some risk.                               an illness.                                   of terminating a pregnancy, prior to
   There is no firm legal basis, however,           2. Studies which represent a deviation     viability. This definition, for the purpose
for parental or guardian consent to par-         from accepted practice, but which are         of this policy, excludes the placenta, fetal
ticipation in research on behalf of sub-         specfically aimed at improved diagnosis,      material which is macerated at the time
jects who are incompetent, by virtue of          prevention, or treatment of a specific ill-   of explusion, a dead fetus, and isolated
age or mental state, to understand the           ness in a patient.

                                     FEDERAL REGISTER, VOL. 38, NO. 221—FRIDAY, NOVEMBER 16, 1973
31740                                                          NOTICES
fetal tissue or organs excised from a dead        L. Supplementary judgment is the          both the ethics of conducting a particular
fetus.                                         judgment made by others to assent, or to     research project, and the adequacy of
   G. Viability of the fetus, means the        refuse to assent, to procedures for which    procedures for protecting the individual
ability of the fetus, after either a spon-     the subject cannot give adequate con-        subjects who will be asked to participate.
taneous delivery or an abortion, to sur-       sent on his or her own behalf. For the       The intention of this policy is to broaden
vive to the point of independently main-       purposes of this document, supplemen-        the scope of review, preclude or resolve
taining vital functions; such a “viable”       tary judgment will refer to judgments        conflicts of interest, and invoke social as
fetus is a premature infant. Determina-        made by local committees in addition to      well as scientific judgments to protect
tion of viability entails a subjective and     the subject’s consent (when possible)        potential subjects who might have
objective judgment by the physician at-        and that of the parents or legal guardian    diminished capacity to consent.
tending labor or examining the product         (where applicable), as to whether or not       The proposed mechanism for protect-
of conception, and must be made by a           a subject may participate in clinical re-    ing subjects with limited ability to give
physician other than the investigator          search. This supplementary judgment is       informed consent culminates in a form of
wishing to use fetal tissue in research. In    to be confirmed by the signature of the      supplementary judgment, which is to be
general, and all other circumstances not-      Chairman of the Protection Committee         supportive and protective of the sub-
withstanding, a beating heart is not suffi-    on the consent form. In accordance with      ject’s best interests and wishes, to the
cient evidence of viability. At least one      the procedures approved by the agency        extent that he or she is capable of for-
additional necessary condition is the          for the Protection Committee, the Chair-     mulating and expressing a judgment. In
possibility that the lungs can be inflated.    man’s signature may be affixed on a          the case of children and the mentally
Without this precondition, no currently        standard consent form, or may need to        infirm, it will supplement their judgment
available mechanisms to initiate or main-      be withheld until the Committee ap-          and that of their parents or guardians.
tain respiration can sustain life; and in      proves the participation of the individual   In the case of competent individuals who
this case, though the heart is beating, the    subject.                                     have restricted autonomy, it will support
fetus or abortus is in fact non-viable.           II. General policy considerations. In     and protect their wishes. Through this
   H. In vitro fertilization is any fertili-   general, clinical research, like medical     mechanism, these subjects will be pro-
zation of human ova which occurs out-          practice, entails some risk to the sub-      tected as fully as possible by community
side the body of the female, either            jects. When the potential subject is un-     review; however, the nature of some re-
through admixture of donor sperm and           able fully to comprehend the risks which     search procedures might be such that, in
ova or by any other means.                     might be involved, or to make the judg-      addition, court review ultimately will be
   I. Prisoner is any individual involun-      ment essential to consent regarding the      required.
tarily confined in a penal institution.        assumption of those risks, current guide       III. Participation of children in re-
The term in intended to encompass indi-        lines suggest obtaining the consent of the   search —A. Policy considerations. Chil-
viduals sentenced to such an institution       parents or legal representative.             dren have generally been considered in-
under a criminal or civil statute, or indi-       Whereas it is clear by law that con-      appropriate subjects for many research
viduals detained by virtue of statutes         sent of a parent or legal representative     activities because of their inability to
which provide alternatives to criminal         is valid for established and generally ac-   give informed consent. There are circum-
prosecution.                                   cepted therapeutic procedures performed      stances, however, which not only justify,
   J. Mentally infirm includes the men-        on a child or an incompetent adult, it is    but even require their participation. Chil-
tally ill, the mentally retarded, the emo-     far from clear that it is adequate for re-   dren do differ from adults in their
tionally disturbed, the psychotic, the         search procedures. In practice, parental     physiologic responses, both to drugs and
senile, and others with impairments of         or guardian consent generally has been       to disease; if the health of children is
a similar nature, residing as patients in      accepted as adequate for therapeutic re-     to be improved, it is necessary to know
an institution, regardless of whether or       search, although the issue has not been      the nature and extent of these differ-
not the individual has been determined         definitively resolved in the courts. When    ences, and to have a full understanding
to be legally incompetent.                     research might expose a subject to risk      of normal patterns of growth and devel-
   K. Informed consent has two elements:       without defined therapeutic benefit or       opment, metabolism, and biochemistry in
comprehension of adequate information          other positive effect on that subject’s      the perinatal, infant, early childhood,
and autonomy of consent. Consent is a          well-being, parental or guardian consent     pubertal and adolescent stages of devel-
continuing process. The person giving          appears to be insufficient.                  opment. Studies of normal physiology
consent must be informed fully of the             In the case of prisoners, confinement     and behavior can also provide significant
nature and purpose of the research and         imposes limitations on freedom of choice     benefit to children suffering from disease;
of the procedures to be used, including        which brings into question their ability     children are the only subjects from whom
identification of those procedures which       to give voluntary consent. A prisoner’s      these data can be obtained. Further-
are experimental, the possible attendant       ability to give consent may be restricted    more, there are diseases which cannot
short or long term risks and discom-           by overt or potential coercion, or by the    be induced in laboratory animals, and
forts, the anticipated benefits to himself     loss of personal autonomy generally con-     occur only rarely, if at all, in human
and/or others, any alternative methods         sidered to result from incarceration it-     adults. In such cases, children are the
of treatment, expected duration of the         self. Therefore, additional protection       only subjects in whom the disease proc-
study, and of his or her freedom to ask        must be afforded this group even though      ess and possible modes of therapy can
any questions and to withdraw at any           an individual’s competency to under-         be studied.
time, should the person wish to do so.         stand what is involved might not be in         The Kefauver-Harris Act l requires
There must also be written evidence of         doubt.                                       that drugs be tested for safety, efficacy
the process used for obtaining informed           The institutionalized mentally infirm     and dosage in children and pregnant
consent, including grounds for belief          are doubly limited: as with children,        women before being approved for use to
that the subject has understood the in-        they might not be competent to make          treat illness in such patients. Food and
formation given and has sufficient ma-         informed judgments, and, as with pris-       Drug Administration (FDA) approval
turity and mental capacity to make such        oners, they are confined under condi-        for the use of a new drug depends
choices and formulate the requisite judg-      tions which limit their civil freedom and    upon submission of proposed label-
ment to consent. In addition, the per-         autonomy. Therefore, their participation     ing for a new drug, which must
son must have sufficient autonomy to           in research requires special protections.    include “adequate directions for use”
choose, without duress, whether or not            The law is not clear on these issues.     and “adequate warnings” as to unap-
to participate. Both the comprehension         Even if the law were clear, however, ethi-   proved uses.2 Acceptance of a new drug
of information and the autonomy of con-        cal questions would remain; specifically,
sent are necessary elements; to the ex-        whether, and under what conditions re-
                                                                                              l Federal
tent that either of these is in doubt, the     search involving these subject groups                    Food, Drug, and Cosmetic Act,
adequacy of informed consent may be in         may proceed. Resolution of these ethical     1962 (FDC Act), 21 U.S.C. Sec. 301 et. seq.
                                                                                              2 FDC Act Sec. 502(f), 21 U.S.C. Sec. 352(f).
doubt.                                         questions requires judgments concerning

                                  FEDERAL REGISTER, VOL. 38, NO. 221—FRIDAY, NOVEMBER 16, 1973
                                                             NOTICES                                                            31741
rests on the adequacy of the research re-    ethically may be subjected? Value judg-        be gained can be obtained in no other
ports submitted with the application to      ments which must be weighed here tran-         way. The investigator must also stipulate
support the proposed labeling.3 Thus, in     scend scientific issues and suggest that       either that the risk to the subjects will
order for a drug to be distributed in in-    the decision requires interaction among        be insignificant, or that although some
terstate commerce for use in children or     individuals in society with diverse train-     risk exists, the potential benefit is sig-
pregnant women, sufficient testing must      ing and perspectives. Further, given the       nificant and far outweighs that risk. In
have taken place in children or pregnant     complexity of the issues and the oppor-        no case will research activities be ap-
women to substantiate claims on the          tunity for conflict among the interests of     proved which entail substantial risk, ex-
label regarding safety, efficacy, and dos-   several parties (the child, the parents or     cept in the case of clearly therapeutic
age for those groups. If the safe and effi-  guardian, the attending physician, and         procedures in which the benefit to the
cacious dosage for children and preg-        the research personnel), decisions re-         patient significantly outweighs the pos-
nant women has not been determined,          garding participation of individual sub-       sible harm. The Ethical Review Board
the label must so state. Thus, participa-    jects in research activities involving chil-   shall review all proposals approved by
tion of children in drug research might      dren should not rest solely with persons       Primary Review Committees involving
be the only means of meeting licensing       directly involved in the research.             children in research activities, except
requirements for new drugs for use in           In order to provide both impartial          when the Primary Review Committees
children, just as studies in pregnant        ethical review of projects and maximum         determine that the subjects are not at
women might be the only means of meet-       protection of individual subjects, two         risk.
ing licensing requirements for new drugs     procedures are proposed in addition to            In addition to reviewing ethical is-
for use in that class of patients.           those currently required: review by an         sues, the Board will review procedures
   When the risk of a proposed study is      Ethical Review Board at the sponsoring         proposed in the research application to
generally considered not significant, and    DHEW agency, and participation by a            be employed by the institution’s Protec-
the potential benefit is explicit, the ethi- Protection Committee at the institution        tion Committee (see below), and may
cal issues need not preclude the partici-    in which the research is to be conducted.      suggest modifications of these procedures.
pation of children in biomedical re-         Both groups will provide community in-         The Board’s recommendation may vary
search. However, the progression from        volvement in decisions and attempt to          from a general concurrence with the pro-
innocuous to noxious, in terms of risk,      balance scientific value and societal ac-      posal, as submitted by the investigator,
is often subtle. Therefore, additional re-   ceptability of proposed research involv-       to a recommendation that each parental
view procedures are necessary for re-        ing children.                                  and subject consent must be obtained
search activities which expose children          B. Ethical Review Board: Ethical re-       with the concurrence of the full Protec-
to risk, in order to provide sharp scru-     view of projects. Each DHEW agency             tion Committee. Any specific recommen-
tiny, vigorous review, and stringent pro-    shall appoint an Ethical Review Board          dations for procedures to be followed by
cedural safeguards for all subjects of       to provide rigorous review of ethical is-      the Protection Committee will be in-
such research.                               sues in research involving human sub-          cluded in the report of the Ethical Re-
   Judgments concerning the ethical          jects by people whose interests are not        view board which will be forwarded to
propriety of research depend partly upon     solely those of the scientific community.      the National Advisory Councils or other
the scientific assessment of the potential   Its functions will include:                    secondary review groups of the agency.
risks and benefits. Risk has several im-         1. Advising the agency on ethical is-      Appropriate information will be provided
portant elements: severity, probability,     sues including review of questions of          by the agency to assist the Protection
frequency, and the timing of possible ad-    policy, and development of guidelines          Committee.
verse effects. While it might not always      and procedures;                                   Inasmuch as the articulation of deci-
be easy to distinguish these elements,           2. Fostering inter-agency coherence        sions might clarify both the objectives
they must be evaluated in the assess-        through cognizance of the policies and         and the assumptions on which they are
ment of risk, and in the determination of    procedures of other agencies;                  based, records of testimony and delibera-
the acceptable limits of specific risk for       3. Reviewing specific proposals or         tions, as well as final decisions, should
an anticipated benefit. The first judg-      classes of proposals submitted to the          be maintained pursuant to existing regu-
ment to be made is whether it is possible    Board by the agency. These will include        lations. Such records will serve addi-
to assess the risk. If studies in animals    proposals stipulated herein as requiring       tionally as the basis for public account-
or adults do not provide sufficient infor-   review by the Board, as well as proposals      ability and will facilitate the review of
mation to assess these elements of risk,                                                    any decision, should such action be re-
                                             submitted on an ad hoc basis by agency
then the research should not be con-                                                        quested.
                                             staff. In addition, the Board may recom-
ducted on children. If the risks can be      mend that certain additional classes of            Members of the Board, which shall
 determined from studies in animal and       research be reviewed.                           number 15, shall be drawn from the gen-
 adult human populations, application to         The acceptability of a research project     eral public, and shall include, for exam-
 children may be considered.                  rests on questions of scientific merit as      ple, research scientists (including social
    In addition to results from investiga-    well as on questions of ethics. The agency     scientists), physicians, lawyers, clergy,
 tions on animals and adult subjects, there   Primary Review Committees are respon-          or ethicists, and other representatives of
 are unknowns which must be considered        sible for evaluating scientific merit and     the public, none of whom shall be em-
 in the weighing of risk to children. These   experimental design. The Ethical Review       ployees of the agency establishing the
 include: (1) differences in physiologic or   Board will be concerned with ethical is-       Board. Appointments shall be made by
 psychologic response from adult pat-         sues and questions of societal accepta-        the agency, which will establish the
 terns; (2) delayed expression of injury      bility in relation to scientific value. In     terms of office and other administrative
 (for example, until puberty); (3) effects    reaching its determination of acceptabil-      procedures of the Board. No more than
 on developing organs (especially the cen-    ity, the Board will rely upon the Primary      1/3 of the members of the Board may be
 tral nervous system); (4) degree of inter-   Review Committees for judgments on             actively engaged in research, develop-
 ference with normal routine required by      scientific merit and design, existence of      ment, or demonstration activities involv-
 the study; and (5) possibility of misuse     prerequisite animal and adult human            ing human subjects.
 of data by institution or school per-        studies, estimated risks and benefits             C. Protection Committee: Protection of
 sonnel.                                      (taking into account the competence            individual subjects. The determination
    Once the severity and probability of      and experience of investigators and the        that it is justifiable to conduct a par-
 risks in a particular study have been        adequacy of their resources), and scien-       ticular investigation in children, how-
 identified, a second judgment must be        tific importance. It will review proposals     ever, does not mean that all children are
 made; given potential benefits of de-        received from these Primary Review             equally appropriate subjects for inclusion
 scribed dimensions, what are the ac-         Committees.                                    in that research. Numerous considera-
 ceptable limits of risk to which children       An investigator proposing research ac-      tions might affect the proper choice of
                                              tivities which expose children to risk         subjects. Therefore, the sponsoring in-
   FDC Act Sec. 505 (b), (d), 21 U.S.C. Sec. must document, as part of the applica-          stitution shall designate a Protection
355 (b), (d).                                 tion for support, that the information to      Committee to oversee: (1) the process of

                                   FEDERAL REGISTER, VOL. 38, NO. 221—FRIDAY, NOVEMBER 16, 1973
31742                                                            NOTICES
selection of subjects who may be in-            consent of either parent is not obtained,          The consent of both parents must be
cluded in the project: (2) the monitor-         written    explanation or       justification   obtained for any research involving the
ing of their continued willingness to par-      should be provided to the Protection            fetus, any statutes to the contrary on
ticipate in the research: and (3) the de-       Committee. Consent of school or institu-        consent for abortion notwithstanding.
sign of procedures to permit intervention       tional authorities is no substitute for par-    Both the mother and the father have
on behalf of the subject, should that           ental concern and consent.                      an interest in the fetus, and legal re-
become     necessary.    This    Committee         2. The child’s consent. An important         sponsibility for it, if it is born. Therefore,
should consider the reasonableness and          addition to the requirement for parental        the father’s consent must be obtained
validity of the consent of the child par-       consent is the consent of the child sub-        for experimental procedures involving
ticipants (see below) as well as that of        ject. Clearly infants have neither the          the fetus; consent of the father may be
the parents, and should assure that the         comprehension nor the independence of           waived if his identity or whereabouts
issue of risk and discomfort has been           judgment essential to consent; older            cannot be ascertained, or if he has been
fully and fairly disclosed to parents and       children might or might not have these          judged mentally incompetent.
subjects. The procedure employed by the         capabilities. Although children might not          IV. Special categories —A. The abor-
institution to achieve these goals will         have the capacity to consent on their own       tus. Prematurity is the major cause of
vary; the latitude for such procedures          to participate in research activities, they     infant death in this country; thus, re-
will be great since it will be related in       must be given the opportunity (so far as        search aimed at developing techniques to
part to the issue of risk. Investigators        they are able) to refuse to participate.        further viability is of utmost importance.
proposing research involving children           The traditional requirement of parental         Such research has already contributed
shall include a description of their            consent for medical procedures is in-           significantly to improvement in the care
planned use of the Protection Committee         tended to be protective rather than coer-       of the pregnant woman and of her fetus.
in their research proposal; the proposed        cive. Thus, while it was held to be un-         In addition, knowledge of fetal drug
use of this Committee will be considered        lawful to proceed merely with the con-          metabolism, enzyme activity, and the
an integral part of the research proposal       sent of the child, but without consent of       development of organs is essential to
under review by the agency. Relevant in-        the parent or legal guardian,5 the reverse      progress in preventing or offsetting cer-
formation arising in the review process,        should also hold. Therefore, in addition        tain congenital defects. After thorough
including information about safety, risk,       to consent of both parents, consent of          research in animal models, it often even-
efficacy, and protection procedures, will       the child subject must also be obtained         tually becomes essential to undertake
be provided to the Protection Committee         when the child has attained the common          studies in the non-viable human fetus.
by the agency supporting the research.          law “age of discretion” of 7 years, unless         The decision of the Supreme Court on
   One member of the Committee shall be         the agency Ethical Review Board specifi-        abortion does not eliminate the ethical
designated a representative for the proj-       cally exempts a project from this require-      issues involved in research on the non-
ect to whom any participant (or parent          ment.                                           viable human fetus. No procedures
of a participant) may go to discuss ques-          3. Exclusions. Despite all the protec-       should be undertaken on the non-viable
tions or reservations concerning the            tions afforded by these procedures, cer-        fetus which clearly affront societal
child’s continued participation in the          tain children are categorically excluded        values. Nevertheless, certain research is
project.                                        from participation in research involving        essential to improve both the chance of
   The signature on the consent form of         risk. These include children with no nat-       survival and the health status of pre-
the Chairman of the Protection Commit-          ural or adoptive parents available to par-      mature infants. Such research must
tee, when all the stipulations and condi-       ticipate in consent deliberations, and          meet ethical standards as well as show
tions identified above have been met, will      children detained by court order in a           a clear relation either to the expecta-
constitute, for DHEW, supplementary             residential facility, whether or not nat-       tion of saving the life of premature in-
judgment on behalf of the child subject.        ural or adoptive parents are available.         fants through the development of rescue
   The institution’s Protection Commit-            E. The fetus. Respect for the dignity        techniques, or to the furthering of our
tee shall be comprised of at least 5 mem-       of human life must not be compromised           knowledge of human development and
                                                whatever the age, circumstance, or ex-          thereby our capacity to offset the dis-
bers so selected that the Committee will                                                        abilities associated with prematurity. It
be competent to deal with the medical,          pectation of life of the individual. There-
                                                fore, all appropriate procedures provid-        is imperative, however, that the investi-
legal, social, and ethical issues involved
in the research, and to represent the           ing protection for children as subjects in      gator first demonstrate that appropriate
community from which the subject popu-          biomedical research must be applied             studies on animals have in fact been ex-
lation is to be drawn. The Committee            with equal rigor and with additional            hausted and that therefore the research
should include members of both sexes.           safeguards to the fetus.                        in question requires that the work be
No more than two of the members may                The recent decision of the Supreme           done on the non-viable human fetus.
be employees of the institution sponsor-        Court on abortion 6 does not nullify the        Specific reasons for this necessity must
ing or conducting the research. The Pro-        ethical obligation to protect the develop-      be identified. A thorough review of the
tection Committee may operate as a sub-         ing fetus from avoidable harm. This             ethical issues in proposed research in-
committee of the Organizational Re-             obligation, along with the right of every       volving the non-viable fetus is of utmost
view Committee. The composition of the          woman to change her decision regarding          importance.
Committee must be approved by the               abortion, requires that no experimental            It must be recognized that consent for
awarding agency.                                procedures entailing risk to the fetus be       abortion does not necessarily entail dis-
   D. Special provisions —1. Consent of         undertaken in anticipation of abortion.         interest on the part of the pregnant
both parents. Even where State law may          Further, since the fetus might be at risk       woman in what happens to the product
permit one parent alone to consent to           in research involving pregnant women,           of conception. Some women feel strongly
medical care, both parents have an inter-       all research involving pregnant women           about what may, or may not, be done to
est in the child, and therefore, consent        must be reviewed by the Ethical Review          the aborted fetus; others do not. In order
of both parents should be obtained be-          Board, unless the Primary Review Com-           to give every woman the opportunity to
fore any child may participate in re-           mittee determines that the research in-         declare her wishes, consent of the preg-
search activities. Since the risks of re-       volves no risk to the fetus. Recruitment        nant woman for application of any re-
search entail the possibility of additional     of pregnant subjects for research re-           search procedures to the aborted fetus
burdens of care and support, the consent        viewed by the Board must involve the            must be secured at the time of admission
of both parents to the assumption of            institution’s Protection Committee in a         to the hospital for the abortion.
those risks should be obtained,4 except         manner approved by the Board, to pro-              Because research on the abortus in-
when the identity or whereabouts of             vide supplementary judgment.                    volves ethical as well as scientific issues,
either cannot be ascertained or either has                                                      all projects involving the abortus must be
been judged mentally incompetent. If the          5 Bonner v. Moran, 75 U.S. App. D.C. 156,     reviewed by the Ethical Review Board,
                                                126 F. 2d 121, 139 A.L.R. 1366 (1941).          and recruitment of individual pregnant
  4   59 Am. Jur. 2d, Sect. 129, p. 229.          6 Roe v. Wade, 410 U.S. 113 (1973).           women for such research must involve

                                       FEDERAL REGISTER, VOL. 38, NO. 221—FRIDAY, NOVEMBER 16, 1973
                                                                NOTICES                                                           31743
the institution’s Protection Committee in       project involving in vitro fertilization,     viewed favorably, and to his advantage,
a manner approved by the Board to pro-          and by recognizing the state of the art, as   by prison authorities (on whom his other
vide supplementary judgment. In addi-           well as societal concerns, propose ap-        few privileges depend) and by the parole
tion to the requirement for maternal            propriate research policy.                    board (on whom his eventual release de-
consent, both the Ethical Review Board             Care must be taken not to bring hu-        pends). This is especially true when the
and the Protection Committee shall, in          man ova fertilized in vitro to viability—     research involves behavior modification
their deliberations, consider the ethical       whether in the laboratory or implanted        and may be termed “therapeutic” with
and social issues surrounding research          in the uterus—until the safety of the         respect to the prisoner. In such instances,
on the non-viable fetus. The Protection         technique has been demonstrated as far        participation inevitably carries with it
Committee must be satisfied that ma-            as possible in sub-human primates. To         the hope that a successful result will in-
ternal consent is freely given and based        this end:                                     crease the subject’s chances for parole.
on full disclosure, each time approved             1. All proposals for research involving    Thus, the inducement involved in thera-
research is conducted on an abortus.            human in vitro fertilization must be re-      peutic research might be extremely diffi-
   In order to insure that research con-        viewed by the Ethical Review Board.           cult to resist: and for this reason, special
siderations do not influence decisions as          2. No research involving the implanta-     protection is necessary for prisoners par-
to timing, method, or extent of a pro-          tion of human ova fertilized in the lab-      ticipating in research, whether or not the
cedure to terminate a pregnancy, no in-         oratory into recipient women should be        research is therapeutic.
vestigator engaged in the research on           supported until the appropriate scientific       The first principle of the Nuremburg
the abortus may take part in these de-          review boards are satisfied that there has    Code requires that subjects of biomedical
cisions. These are decisions to be made         been sufficient work in animals (includ-      research must be “so situated as to be
by the woman and her physician.                 ing sub-human primates) to demon-             able to exercise free power of choice”
   The attending physician, not the in-         strate the safety of the technique. It is     concerning their participation. Whether
vestigator, must determine the viability        recommended that this determination of        prisoners can be considered to be “so
of the abortus at the termination of preg-      safety include studies of natural born        situated” is ultimately a matter for the
nancy. If there is a reasonable possibility     offspring of the products of in vitro         courts and the legislatures to resolve. In
that the life of the fetus might be saved,      fertilization.                                the meantime, it must be recognized that
experimental and established methods               3. No implantation of human ova            where liberty is limited, and where free-
may be used to achieve that goal. Artifi-       fertilized in the laboratory should be        dom of choice is restricted, there is a
cial life-support techniques may be em-         attempted until guidelines are developed      corresponding limitation of the capacity
ployed only if the physician of record de-      governing the responsibilities of the do-     to give truly voluntary consent. Although
termines that the fetus might be viable.        nor and recipient “parents” and of re-        the prisoner might be adequately in-
If the physician determines that the            search institutions and personnel.            formed, and competent to make judg-
fetus is not viable, it is not acceptable to       V. Prisoners —A. Policy considerations.    ments, the voluntariness of the person’s
maintain heart beat or respiration arti-        Clinical research often requires the par-     consent remains open to question. This
ficially in the abortus for the purpose of      ticipation of normal volunteers; for ex-      policy statement is designed to provide
research. Experimental procedures which         ample in the early stages of drug or          additional protections to prisoners par-
of themselves will terminate respiration        vaccine evaluation. Sometimes, the need       ticipating in research.
and heart beat may not be undertaken.           for standardization certain variables, or        The mission of the Department of
   This policy and these protections apply      for monitoring responses over an ex-          Health, Education, and Welfare does not
with equal force to the products of spon-       tended period of time, requires that the      include rendering judgments on the ad-
taneous abortions.                              subjects of research remain in a con-         ministration of justice or the manage-
   B. The products of in vitro fertilization.   trolled environment for the duration of       ment of the correctional system. At the
In the interest of improving human              the project. Prisoners may be especially      same time, the Department should not
health and development, the biology of          suitable subjects for such studies, since,    support activities which take unethical
human fertilization and the early events        unlike most adults, they can donate their     advantage of those who are under the
surrounding this phenomenon, including          time to research at virtually no cost to      jurisdiction of the courts and who, for
implantation, should be studied. To the         themselves. However, the special status       that reason, lack some of the usual de-
extent that in vitro studies of human           of prisoners requires that they have          fenses to their personal integrity. Partici-
fertilization might further this aim, they      special protection when they participate      pation of prisoners in the research activ-
are permissible at the present time with-       in research.                                  ities of the DHEW in the pursuit of medi-
in the limits outlined below.                      While there is no legal or moral objec-    cal knowledge might be beneficial to all
   Current technology limits the in vitro       tion to the participation of normal vol-      concerned, but the relationship which
development of the human fertilized             unteers in research, there are problems       involves a class of persons with dimin-
ovum to a period of several days. This is       surrounding the participation of volun-       ished autonomy requires careful super-
a rapidly advancing field of biomedical         teers who are confined in an institution.     vision.
research, however, and the time might           Many aspects of institutional life may           Many prisoners are strongly motivated
come when it is possible to extend in           influence a decision to participate; the      to participate in research, and view as
vitro development beyond the stage of           extent of that influence might amount to      unfair suggestions that they be denied
early cell division and possibly even to        coercion, whether it is intended or not.      this opportunity. Unless society, through
viability.                                      Where there are no opportunities for          its judicial and legislative bodies, decides
   It is contrary to the interests of so-       productive activity, research projects        that such participation should be halted,
ciety to set permanent restrictions on          might offer relief from boredom. Where        it is essential to develop mechanisms to
research which are based on the suc-            there are no opportunities for earning        protect those who may participate, or
cesses and limitations of current tech-         money, research projects offer a source       who are now participating, from the co-
nology. Still, it is necessary to impose        of income. Where living conditions are        ercive aspects of incarceration which
restraints prospectively in order to pro-       unsatisfactory, research projects might       diminish their capacity for voluntary
vide reasonable protections, while at the       offer a respite in the form of good food,     consent. Pursuant to the obligation to
same time permitting scientific advance-        comfortable bedding, and medical atten-       protect the rights of all subjects partici-
ments which might well benefit society.         tion. While this is not necessarily wrong,    pating in research conducted under its
A mechanism is required to weigh, at any        the inducement (compared to the depri-        auspices, the DHEW is proposing special
given time, the state of the art, a specific    vation) might cause prisoners to offer to     guidelines for the protection of prison-
proposal, legal issues, community stand-        participate in research which would ex-       ers as subjects in any biomedical or be-
ards, and the availability of guidelines to     pose them to risks of pain or incapacity      havioral research.
govern the research situation. This             which, under normal circumstances, they          Two aspects of research involving
mechanism is provided by the Ethical            would refuse. In addition, there is al-       prison populations require special review
Review Board. Ultimately, the Board             ways the possibility that the prisoner will   and procedural safeguards in addition to
will determine the acceptability of a           expect participation in research to be        those provided by current DHEW policies.

                                    FEDERAL REGISTER, VOL. 38, NO. 221—FRIDAY, NOVEMBER 16, 1973
31744                                                         NOTICES

First, when research is conducted under       overseeing the selection of subjects who         D. Payment to prisoners. The amount
the auspices of a commercial manufac-         may be included in a research project to      paid for participation in research will
turer or an individual investigator, it is    assure that their consent is as voluntary     vary according to the risks and discom-
not always subject to review by an Or-        as possible under the conditions of con-      forts involved, and the other employment
ganizational Review Committee, as is re-      finement.                                     opportunities in the facility in which the
quired for similar research conducted at         Consent is a continuing process. To        research is to be conducted. The specific
a hospital or a university. Thus, local       assure the voluntariness of consent, sub-     amount for each project will be deter-
review has not heretofore been required       jects must be able to withdraw from           mined by the Organizational Review
for ethical considerations or for specific    the research project without prejudice.       Committee, which will forward its rec-
problems related to the population or in-     Each Protection Committee shall estab-        ommendation as part of the application
stitution which is to be directly involved.   lish such a withdrawal mechanism.             to the sponsoring agency. The amount
Second, because of the loss of individual        The duties of the Protection Commit-       paid shall provide a compensation for
dignity, the limitations of personal free-    tee, therefore, shall include:                services, but shall not be so great as to
dom, and the possibility of real or poten-       1. Reviewing the information given         constitute undue inducement to partici-
tial coercion which may accompany con-        the potential subjects, with special atten-   pate.
finement in an institution, special safe-     tion to: adverse effects, the importance         Any reduction of sentence as a conse-
guards must be provided to mitigate the       of reporting all deviations from normal       quence of participation in research shall
inequalities of bargaining power between      function, the continuing option of with-      be comparable to other opportunities at
the prisoners and those who are in posi-      drawing from participation at any time,       the facility for earning such a reduction.
tions of authority. While it is important     and the identification of a member of the        Any subject who is required by the in-
that prisoners have the opportunity to        committee who will be available, at rea-      vestigator or prison physician to with-
participate in research, it is equally im-    sonable intervals upon request, for con-      draw, for medical reasons, before com-
portant that they not feel compelled to       sultation regarding the research project.     pletion of the investigation, shall con-
do so.                                        All of this information shall appear on       tinue to be paid for a period to be deter-
   B. Organizational Review Committee.        the consent form, a copy of which will        mined by the Protection Committee in
All research involving prisoners must be      be given to each participant. When oral       consultation with the investigator. This
conducted at an accredited correctional       representations are made procedures de-       does not apply to subjects who withdraw
facility (see Section F, below) and be re-    scribed under DHEW regulations shall          for other reasons. Any disputes regarding
viewed initially, and on a continuing         be followed.                                  certification of withdrawal for medical
basis, either by the Organizational Re-          2. Overseeing the process of selection     reasons shall be heard and resolved by
view Committee of that correctional fa-       of subjects who may be included in the        the Protection Committee.
cility or by the Organizational Review        research, to the extent stipulated in the        Prisoners who serve on the Protection
Committee of the institution sponsoring       recommendation of the Organizational          Committee shall be paid an amount con-
the research. The Organizational Review       Review Committee. This may vary from          sistent with that received by the research
Committee shall have the duties and re-       overall approval of the recruitment proc-     subjects.
sponsibilities identified in current DHEW     ess, to reviewing a sample of subject            E.     Accreditation.  The    Secretary,
regulations. In addition, for each project,   selections, to interviewing as a full Com-    DHEW, shall establish standards for ac-
it shall determine the adequacy of clinic     mittee each individual subject to be in-      creditation of correctional facilities of-
or hospital facilities for the particular     cluded in the project.                        fering to act as sites for the performance
activity to be conducted, assess the ap-         3. Visiting the institution on a regular   of clinical research, or offering to act as
propriateness of the subject population       basis to invite questions, to monitor the     a source of volunteer subjects for clinical
for that activity, and weigh the questions    progress of the research, and to assess       research when the research is supported
of scientific importance, social need, and    the continued willingness of subject par-     in whole or in part by Departmental
ethical acceptability. In addition to the     ticipation. The frequency of these visits     funds or the research is to be performed
foregoing, the Organizational Review          will be determined by the nature of the       in compliance with requirements of Fed-
Committee shall have the following du-        research, and any recommendations of          eral statutes.
ties, with respect to research involving      the Organizational Review Committee.             The review for certification shall in-
prisoners as subjects:                        Depending upon the circumstances and          clude, but not be limited to:
   1. To review and approve or modify         the number of subjects involved, these           1. Standard of living in the prison
the process proposed by the principal         visits may be made either on a rotating       facility.
investigator for involvement of the Pro-      basis by various members of the Commit-          2. Other opportunities for employ-
tection Committee (see below) in over-        tee, or by the full Committee.                ment and/or constructive activity, either
seeing the selection of subjects who may         4. Maintaining records of its activities   within the prison, or in a work-release
be included in the research, and the proc-    including contacts initiated by subjects      program.
ess of obtaining their voluntary and in-      in the project between regular site visits.      3. Adequacy of (a) medical care for
formed consent.                               These records shall be made available to      the general prison population (so that
   2. To set rates of remuneration, if any,   the agency upon request.                      participation in research is not the only
consistent with the expected duration            The Protection Committee shall be          means of obtaining medical attention),
and discomfort or risk of the proposed        comprised of at least 5 members so se-        and (b) the proposed methods for main-
study, and consistent with other oppor-       lected that the Committee will be compe-      taining medical records and for protect-
tunities for employment, if any, at the       tent to deal with the medical, legal, so-     ing the confidentiality of those records.
facility in question.                         cial, and ethical issues involved. No more       4. The nature, structure, function, and
   3. To monitor the progress of the re-      than 1/ of the members shall be scientists
                                                      3                                     composition of the Organizational Re-
search as required by the sponsoring          engaged in biomedical research or physi-      view Committee (whether located at the
DHEW agency.                                  cians; at least 1 shall be a prisoner or a    prison or at the institution sponsoring
   The recommendations of this Com-           representative of an organization con-        the research) which is to review clinical
mittee, along with a report describing        cerned with the prisoners’ interests; no      research in that correctional facility.
any site visits, shall be included with the   more than 1 (except prisoners or their           The Secretary shall also set general
investigator’s application to the agency.     representatives) shall have any affiliation   guidelines to assist the Organizational
For facilities which have filed no gen-       with the prison facility or with the unit     Review Committees in determining rates
eral assurance, composition as well as        of government having jurisdiction over        of remuneration, and shall indicate
recommendations of the Organizational         the facility, with the exception of persons   groups who may be considered to repre-
Review Committee will be considered an        employed by the department of education       sent the prisoners’ interests for the pur-
integral part of the proposal in the          of a relevant jurisdiction in a teaching      pose of appointment to membership on
agency review.                                capacity. The composition and the inves-      the Protection Committee. No institution
   C. Protection Committee. The primary       tigator’s proposed use of the Committee       shall be accredited if research, whether
function of the Protection Committee is       must be reviewed and approved by the          or not supported by funds from the
to provide supplementary judgment by          DHEW agency.                                  DHEW, is conducted under its auspices,

                                  FEDERAL REGISTER, VOL. 38, NO. 221—FRIDAY, NOVEMBER 16, 1973
                                                                NOTICES                                                              31745

or by members of its staff, which is not         mation can be obtained only from those        ticular DHEW grant or contract, he may
in conformity with these guidelines. No          subjects; or the studies concern institu-     require that said grant or contract be ter-
                                                 tional life per se. With these exceptions,    minated or suspended in the manner pre-
DHEW funds will be granted for research                                                        scribed in applicable grant or procurement
in institutions lacking such accreditation.      the general rule is that the participation    regulations.
   F. Special provisions. 1. Persons de-         of the mentally infirm as subjects in re-        If, in the judgment of the Secretary, an
tained in a correctional facility while          search is not acceptable.                     organization fails to discharge its responsi-
awaiting sentence, or in a hospital fa-             B. Ethical review of projects and pro-     bilities for the protection of the rights and
cility for pre-sentence diagnostic obser-        tection of subjects. In instances in which    welfare of the subjects in its care, whether
vation, are excluded from participation          a research protocol requires the partici-     or not DHEW funds are involved, he may,
in research.                                     pation of mentally infirm subjects, the       upon reasonable notice to the organization
                                                 research must be overseen by a Protec-        of the basis for such action, determine that
    2. A child may not be included as a                                                        its eligibility to receive further DHEW grants
subject in research involving risk if he         tion Committee in the manner described        or contracts involving human subjects shall
is detained in an institutional setting          in Section III–C, pertaining to children.     be terminated. Such disqualification shall
pursuant to a court order, whether or not        This Protection Committee must be sup-        continue until it is shown to the satisfaction
the parents and the child have consented         ervised on a continuing basis, as de-         of the Secretary that the reasons therefor
to the child’s participation.                    scribed in Section V–B, by the Organiza-      no longer exist.
   VI. The mentally infirm. —A. Policy           tional Review Committee of the institu-          If, in the judgment of the Secretary, an
considerations.      The     institutionalized   tion in which the research is to be con-      individual serving as principal investigator,
mentally infirm are doubly limited with          ducted or of the institution sponsoring       program director, or other person having
                                                 the research.                                 responsibility for the scientific and technical
respect to participation in research ac-                                                       direction of a project or activity, has failed
tivities. First, as with children, they             VII. General provisions. These pro-
                                                                                               to discharge his responsibilities for the pro-
might lack the clear capacity to com-            visions apply to all research activities      tection of the rights and welfare of human
prehend relevant information, and to             covered by this policy.                       subjects in his care, the Secretary may, upon
make informed judgments concerning                  A. Referrals to the Ethical Review         reasonable notice to the individual of the
their participation. Second, as with pris-       Board. Whenever a Primary Review              basis for such action, determine that such
oners, they experience a diminished              Committee, secondary review group, or         individual’s eligibility to serve as a princi-
sense of personal integrity as a result of       the agency staff perceives an apparent        pal investigator or program director or in
                                                 and significant question of ethics or an      another similar capacity shall be terminated.
confinement in an institution. Such con-                                                       Such disqualification shall continue until it
finement restricts their freedom of choice       unusual element of risk—whatever the          is shown to the satisfaction of the Secretary
and imposes elements of coercion, which          subject group involved—the research           that the reasons therefor no longer exist.7
limit their capacity to give truly volun-        proposal in question may be forwarded            In reaching a determination on com-
tary consent. In addition, the mentally          to the Ethical Review Board for an opin-      pliance, with respect to subjects with
infirm who are confined in institutions          ion. In addition to offering an opinion of    limited capacity for consent, the Secre-
have more pressures to cooperate with            acceptability from an ethical viewpoint,      tary will consider the extent and the
custodial authorities than do prisoners,         the Board may choose to recommend the         nature of the procedures by which the
for their release might depend entirely          establishment of a Protection Commit-         institution offers protection in all studies
upon their behavior and on the impres-           tee, and suggest guidelines for its opera-    conducted in or by that institution re-
sion they make upon those having the             tion.                                         gardless of the source of funds, with the
power to make decisions concerning ter-             B. Procedures requiring special con-       expectation that there shall be an ethical
mination of their confinement.                   sideration. All other recommendations         review similar to that required of the
   Legal guardians, who have authority           notwithstanding, DHEW may identify             agency Ethical Review Board (III–B).
to consent for medical treatment, might          certain procedures which: (1) Require         The existence of a Protection Commit-
have interests in the matter which do            Protection Committee review of the se-        tee, overseen by an Organizational Re-
not necessarily coincide with those of           lection of each individual subject; (2)       view Committee and acting to afford sup-
the patient. Long-term management of             are acceptable for stipulated subjects         plementary judgment, will be accepted
patients with mental disabilities is ex-         only if approved by affirmative declara-      as evidence of responsibility in this
pensive and time-consuming. Any pro-             tory judgment of a court of competent         regard.
posal which might reduce either the ex-          jurisdiction; or (3) are unacceptable.           F. Confidentiality of information and
pense or the supervision required in                C. Research conducted in Foreign           records. Nothing in this policy shall be
 caring for such persons might be appeal-        Countries. All regulations governing re-      construed as permitting the release of
ing, whether or not there is correlative         search conducted in the United States         confidential research protocols nor the
benefit to the patient. This is certainly        apply to research conducted in foreign        violation of State law applicable to the
the case in projects offering new ther-          countries under DHEW auspices, and            confidentiality of individual medical
 apy; it might also occur, albeit in a more      the ethical review must be of equal rigor.    records.
 subtle form, where free medical or cus-            There are sometimes special con-              VIII. Draft additions to proposed reg-
 todial services are perceived to be con-        straints encountered in foreign settings.     ulations (See FEDERAL REGISTER, Vol. 38,
 tingent upon the patient’s participation        Therefore, in addition to the require-        No. 194, Part 2, Tues., Oct. 9, 1973, pp.
 as a subject in research.                       ment that consent procedures for re-          27882–27885).
    The courts have begun to recognize           search to be conducted abroad conform            To amend the proposed Part 46 of Sub-
 that persons confined in institutions           with the policy and regulations set forth     title A of Title 45 of the Code of Fed-
 might not be able to give truly voluntary       in this document, there must be written       eral Regulations by deleting §§ 46.20
 consent in such matters. It is important        assurance that the proposed research          through 46.23, redesignating §§ 46.1
 to recognize, as well, that persons en-         enjoys local acceptance, and offends no       through 46.19 thereof as Subpart A, and
 cumbered with the economic or custodial         local ethical standards.                      adding the following new Subparts B
 responsibility for the mentally infirm             D. Research submitted pursuant to          through F:
 might not be sufficiently objective to          DHEW regulatory requirements. Re-              SUBPART B—ADDITIONAL PROTECTIONS FOR
 make judgments which are fully in the            search or testing which is performed            CHILDREN INVOLVED AS SUBJECTS IN DHEW
 best interest of the institutionalized per-     pursuant to or in fulfillment of any reg-        ACTIVITIES
 son.                                            ulation issued by any agency of the           Sec.
    The circumstances are limited under          DHEW will be acceptable to the govern-        46.21   Applicability.
 which it is justifiable to include the men-     ment only if conducted in compliance          46.22   Purpose.
 tally infirm as subjects in biomedical re-      with these procedures and regulations,        46.23   Need for legally effective consent.
 search. These circumstances include                E. Clinical research not funded by         46.24   Definitions.
 projects in which: the proposed research                                                      46.25   Ethical Review Board: Composition;
                                                 DHEW.                                                  Duties.
 concerns diagnosis, treatment, preven-            If, in the judgment of the Secretary, an
 tion, or etiology of the disability from        organization has failed to comply with the      7 FEDERAL REGISTER, Vol. 38, No. 194, Part 2,
 which they suffer; the necessary infor-         terms of this policy with respect to a par-   Tuesday, October 9, 1973, § 46.22, p. 27885.

                                    FEDERAL REGISTER, VOL. 38, NO. 221—FRIDAY, NOVEMBER 16, 1973
       No. 221—Pt. II——2
31746                                                               NOTICES
Sec.                                              under might be unable fully to comprehend             (d) In      decisions   regarding   activities
46.26 Protection Committees; Composition;         the risks which might be involved and are          covered by this subpart, the agency shall
        Duties.                                   legally incapable of consenting to their par-      take into account the recommendations of
46.27 Certain children excluded from par-         ticipation in such activities.                     the Board.
        ticipation in DHEW supported ac-             Section 46.23 Need for legally effective           Section 46.26 Protection Committees; com-
        tivities.                                 consent. Nothing in this subpart shall be          position; duties. (a) No activity covered by
46.28 Activities to be performed outside the      construed as indicating that compliance with       this subpart will be approved unless it pro-
        United States.                            the procedures set forth herein will neces-        vides for the establishment by the applicant
SUBPART C—ADDITIONAL PROTECTIONS FOR              sarily result in a legally effective consent       of a Protection Committee, composed of at
  CERTAIN CLASSES OF DHEW ACTIVITIES              under applicable State or local law to a sub-      least five members so selected that the Com-
                                                  ject’s participation in any activity; nor in       mittee will be competent to deal with the
46.31   Applicability.                            particular does it obviate the need for court      medical, legal, social and ethical issues in-
46.32   Purpose.                                  approval of such participation where court         volved in the activity. None of the members
46.33   Definitions.                              approval is required under applicable State        shall have any association with the pro-
46.34   Duties of the Ethical Review Board.       or local law in order to obtain a legally ef-      posed activity, and at least one-half shall
46.35   Maternal consent to activities involv-    fective consent.                                   have no association with any organization or
          ing the abortus.                           Section 46.24 Definitions. As used in this      individual conducting or supporting the
46.36   Additional conditions for activities      subpart:                                           activity. No more than one-third of the
          involving the abortus.                     (a) “DHEW activity” means:                      members shall be individuals engaged in
46.37   Prohibition on certain activities in-        (1) The conduct or support (through             research,     development,    or   demonstration
          volving pregnant women where the        grants, contracts, or other awards) of bio-        activities involving human subjects. The
          fetus may be adversely affected.        medical or behavioral research involving           composition of the Protection Committee
46.38   Parental consent to activities which      human subjects; or                                 shall be subject to DHEW approval.
          may affect the fetus.                      (2) Research, development, or demon-               (b) The duties of the Protection Commit-
46.39   Activities to be performed outside the    stration activities regulated by any DHEW          tee, proposed by the applicant, and reviewed
          United States.                          agency.                                            by the agency including the Ethical Review
                                                     (b) “Subject at risk” means any individ-        Board shall be to oversee: (1) The selection
SUBPART D—ADDITIONAL PROTECTIONS FOR                                                                 of subjects who may be included in the
  PRISONERS INVOLVED AS SUBJECTS IN DHEW          ual who might be exposed to the possibility
                                                  of harm—physical, psychological, sociologi-        activity; (2) the monitoring of the subject’s
  ACTIVlTIES                                      cal, or other—as a consequence of partici-         continued willingness to participate in the
Sec.                                              pation as a subject in any DHEW activity           activity; (3) the design of procedures to per-
46.41   Applicability.                            which goes beyond the application of those         mit intervention on behalf of one or more
46.42   Purpose.                                  established and accepted methods necessary         of the subjects if conditions warrant: (4) the
46.43   Definitions.                              to meet his needs.                                 evaluation of the reasonableness of the par-
46.44   Additional duties of Organizational          (c) “Child” means an individual who has         ents’ consent and (where applicable) the
          Review Committee where prisoners        not attained the legal age of consent to           subject’s consent; and (5) the procedures for
          are involved.                           participate in research as determined under        advising the subject and/or the parents con-
46.45   Protection Committees; Duties; Com-       the applicable law of the jurisdiction in          cerning the subject’s continued participation
          position.                               which such research is to be conducted.            in the activity. Each subject and his or her
46.46   Prohibition on participation in activi-      (d) “DHEW” means the Department of              parent or guardian will be informed of the
          ties prior to conviction.               Health, Education and Welfare.                     name of a member of the Protection Com-
46.47   Remuneration to subjects.                     Section 46.25 Agency Ethical Review            mittee who will be available for consulta-
46.48   Accreditation.                            Board; composition; duties. (a) The head of        tion concerning the activity.
46.49   Activities to be performed outside the    each agency shall establish an Ethical Re-            (c) The Protection Committee shall estab-
          United States.                          view Board, hereinafter referred to as the         lish rules of procedure for conducting its
                                                  “Board,” to review proposals for research, de-     activities, which must be reviewed by DHEW,
SUBPART E—ADDITIONAL PROTECTIONS FOR THE                                                             and shall conduct its activities at convened
  INSTITUTIONALIZED MENTALLY INFIRM IN-           velopment, and demonstration activities to
                                                  which this subpart is applicable, as well as       meetings, minutes of which shall be prepared
                                                  to advise him or her on matters of policy          and retained.
46.51 Applicability.                              concerning protection of human subjects.              Section 46.27 Certain children excluded
46.52 Purpose.                                    The Board shall be composed of research            from participation in DHEW activities. A
46.53 Definitions.                                scientists (biomedical, behavioral, and/or         child may not be included as a subject in
46.54 Limitations on activities involving the     social), physicians, lawyers, clergy, ethicists,   DHEW activities to which this subpart is ap-
        institutionalized mentally infirm.        and representatives of the public. It shall        plicable if:
46.55 Additional duties of Organizstional         consist of 15 members appointed by the                (a) The child has no known living parent
        Review Committee where the men-           agency head from outside the Federal Gov-          who is available and capable of participating
        tally infirm are involved.                ernment. No more than one-third of the             in the consent process: Provided, That this
46.56 Protection Committees; Duties; Com-         members may be individuals engaged in re-          exclusion shall be inapplicable if the child
        position.                                 search,     development,    or   demonstration     is seriously ill, and the proposed research is
46.57 Activities to be performed outside the      activities involving human subjects.               designed to substantially alleviate his con-
        United States.                               (b) It shall be the function of the Board       dition; or
        SUBPART   F—GENERAL   PROVISIONS          to review each proposed activity to which             (b) The child has only one-known living
                                                  this subpart applies, and advise the agency        parent who is available and capable of par-
46.61 Applicability.                              concerning the acceptability of such activ-        ticipating in the consent process, or only one
46.62 Organization’s records.                     ities from the standpoint of societal need         such parent, and that parent has not given
46.63 Reports.                                    and ethical considerations, taking into ac-        consent to the child’s participation in the
46.64 Early termination of awards; sanctions      count the assessment of the appropriate            activity; or
        for noncompliance.                        Primary Review Committees as to: (1) The              (c) Both the child’s parents are available
46.65 Conditions.                                 potential benefit of the proposed activity,        and capable of participating in the consent
                                                  (a) scientific merit and experimental de-          process, but both have not given such con-
  AUTHORITY: 5 U.S.C. 301.                        sign, (3) whether the proposed activity
                                                  entails risk of significant harm to the sub-       sent;
SUBPART B—ADDITIONAL PROTECTIONS FOR              ject, (4) the sufficiency of animal and adult         (d) The child is involuntarily confined in
  CHILDREN INVOLVED AS SUBJECT IN DHEW            human studies demonstrating safety and             an institutional setting pursuant to a court
  ACTIVITIES                                      clear potential benefit of the proposed pro-       order, whether or not the parents and child
   Section 46.21 Applicability. (a) The regu-     cedures and providing sufficient information       have consented to the child’s participation in
lations in this subpart are applicable to all     on which to base an assessment of the risks,       the activity; or
Department of Health, Education, and Wel-         and (5) whether the information to be                 (e) The child has not given consent to his
fare research, development, or demonstra-         gained may be obtained from further animal         or her participation in the research:        Pro-
tion activities in which children may be at       and adult human studies.                           vided, That this exclusion shall be inapplica-
risk.                                                (c) The Board shall review the procedures       ble if the child is 6 years of age or less or
   (b) The requirements of this subpart are       proposed by the applicant to be followed by        if explicitly waived by the DHEW; or
in addition to those imposed under subpart        the Protection Committee, provided for in             (f) The Protection Committee established
A of this part.                                   § 46.26 of this subpart, in carrying out its       under § 46.26 of this subpart has not reviewed
   Section 46.22 Purpose. It is the purpose       functions as set forth in § 46.26. In addition,    and approved the child’s participation in the
of this subpart to provide additional safe-       the Board may recommend additional func-           activity.
guards in reviewing activities to which this      tions to be performed by the Protection               Section 46.28 Activities to be performed
subpart is applicable inasmuch as the poten-      Committee in connection with any particular        outside the United States. In addition to sat-
tial subjects in activities conducted there-      activity.                                          isfying all other applicable requirements in

                                      FEDERAL REGISTER, VOL. 38, NO. 221—FRIDAY, NOVEMBER 16, 1973
                                                                     NOTICES                                                                 31747
this subpart, an activity to which this sub-       onstrating the clear potential benefit of the         (2) research, development, or demonstra-
part in applicable, which is to be conducted       proposed procedures and (4) whether the            tion activities regulated by any DHEW
outside the United States, must include            information to be gained may be obtained           agency.
written documentation satisfactory to DHEW         from further animal or adult human studies.           (b) “Prisoner” means any individual in-
that the proposed activity is acceptable under         (b) The Board may recommend the estab-         voluntarily confined in a penal institution.
the legal, social, and ethical standards of the    lishment by the sponsoring institution of a        The term is intended to encompass individ-
locale in which it is to be performed.             Protection Committee to carry out such func-       uals sentenced to such an institution under
                                                   tions as the Board deems necessary.                a criminal or civil statute and also individ-
  SUBPART C—ADDITIONAL PROTECTION FOR                  Section 46.35 Maternal consent to activ-       uals detained by virtue of statutes which
   CERTAIN CLASSES OF DHEW ACTIVITIES              ities involving the abortus. (a) No activity to    provide alternatives to criminal prosecution.
    Section 46.31 Applicability. (a) The regu-     which this subpart is applicable may involve          (c) “DHEW” means the Department of
lations in this subpart are applicable to all      an abortus or a non-viable fetus unless ma-        Health, Education, and Welfare.
Department of Health, Education, and Wel-          ternal consent has been obtained.                     Section 46.44 Additional duties of Organi-
fare research, development, or demonstration           (b) No activity to which this subpart is       zational Review Committee where prisoners
activities:   (1) Involving pregnant women,        applicable may involve an abortus or a non-        are involved. (a) In carrying out its responsi-
unless there is a finding by DHEW that the         viable fetus unless: (1) Individuals involved      bilities under subpart A of this part for activ-
activity will have no adverse effect on the        in the activity will have no part in the de-       ities also covered by this subpart, the Organi-
fetus, or is clearly thereapeutic with respect     cision as to timing, method, or extent of the      zational Review Committee provided for un-
to the fetus involved, (2) involving the abor-     procedure used to terminate the pregnancy,         der subpart A shall also certify: (1) That
tus or the non-viable fetus, or (3) involv-        or in determining viability of the fetus at        there will be no undue inducements to par-
ing in vitro fertilization of human ova.           the termination of the pregnancy; (2) vital        ticipation by prisoners as subjects in the ac-
    (b) Nothing in this subpart shall be con-      functions of the abortus will not be main-         tivity, taking into account among other fac-
strued as indicating that compliance with          tained artificially for purposes of research;      tors, the sources of earnings generally avail-
the procedures set forth herein will in any        and      (3)  experimental procedures which        able to the prisoners as compared with those
way render inapplicable pertinent State or         would terminate heart beat or respiration in       offered to participants in the activity, (2)
local laws bearing upon activities covered         the abortus will not be employed.                  that the clinic and hospital facilities are ade-
by this subpart.                                       Section 46.37 Prohibition on certain ac-       quate for the proposed activity, (3) that all
    (c) To the extent the requirements of sub-     tivities involving pregnant women where the        aspects of the activity would be appropriate
part A of this part are applicable to activities   fetus may be adversely affected. The Board         for performance on nonprisoners, and (4)
also covered by this subpart, the require-         shall review all research, development, and        that no prisoner will be offered any reduction
ments of this subpart are in addition to           demonstration activities involving pregnant        in sentence or parole for participation in
those imposed under subpart A.                     women. No activity to which this subpart is        such activity which is not comparable to that
    Section 46.32 Purpose. It is the purpose of    applicable may involve a pregnant woman if         offered for other activities at the facility not
this subpart to provide additional safeguards      the Primary Review Committee finds that the        of a research, development, demonstration or
in reviewing activities to which this subpart      fetus might be adversely affected, unless the      similar nature.
is applicable to assure that they conform to       primary purpose of the activity is to benefit         (b) In addition, the Organizational Re-
appropriate ethical standards and relate to        that fetus. In addition, no activity to which      view Committee shall have the following
important societal needs.                          this subpart is applicable may involve preg-       duties: (1) To review, approve, or modify the
    Section 46.33 Definitions. As used in this     nant women unless all the requirements of          procedures proposed for the Protection Com-
subpart:                                           this subpart are satisfied.                        mittee in carrying out its functions as set
    (a) “DHEW” means the Department of                 Section 46.38 Parental consent to activi-      forth in § 46.45; (2) To recommend any addi-
Health, Education, and Welfare.                    ties which might affect the fetus. No activity     tional functions to be performed by the Pro-
    (b) “DHEW activity” means:                     involving a pregnant woman which might             tection Committee in connection with a par-
    (1) The conduct or support (through            affect the fetus but which nevertheless is         ticular activity; (3) To set rates of remunera-
grants, contracts, or other awards) of bio-        permissible under § 46.37 shall be conducted       tion, if any, consistent with the anticipated
medical or behavioral research involving hu-       unless maternal consent has been obtained,         duration, discomfort, and/or risk of the ac-
man subjects; or                                   as well as the consent of the father if he is      tivity but not in excess of that paid for other
    (2) Research, development, or demonstra-       available and capable of participating in the      employment generally available to inmates
tion activities regulated by any DHEW              consent process.                                   of the facility in question; and (4) To carry
agency.                                                Section 46.39 Activities to be performed       out such other responsibilities as may be
    (c) “Board” means the Board established        outside the United States. In addition to          stipulated by DHEW in the contract or grant
under § 46.25.                                     satisfying all other applicable requirements       award.
    (d) “Protection Committee” means a com-        in this subpart, activities to whim this sub-         (c) Activities to which this subpart is ap-
mittee referred to in § 46.30.                     part is applicable, which are to be conducted      plicable must provide for the designation of
    (e) “Pregnancy” means the period of time       outside the United States, must include writ-      an Organizational Review Committee, where
from implantation of a fertilized ovum until       ten documentation satisfactory to DHEW             no such Committee has been established
delivery.                                          that the proposed activity is acceptable under     under subpart A.
    (f) “Fetus” means the product of concep-       the legal, social, and ethical standards of the       Section      46.45   Protection   Committees;
tion from implantation until delivery.             locale in which it is to be performed.             duties; composition. (a) No activity covered
    (g) “Abortus” means the fetus when it has      SUBPART D—ADDITIONAL PROTECTIONS FOR               by this subpart will be approved unless it
been expelled whole, whether spontaneously           PRISONERS INVOLVED AS SUBJECTS IN DHEW           provides for the establishment of a Protec-
or as a result of medical or surgical inter-         ACTIVITIES                                       tion Committee to carry out the following
vention to terminate a pregnancy, prior to                                                            functions, as well as any others recommended
viability. This definition, for the purpose of        Section 46.41 Applicability. (a) The regu-      by the Organizational Review Committee or
this policy, excludes the placenta, fetal          lations in this subpart are applicable to all      by DHEW: (1) Reviewing the procedure for
material which is macerated at the time of         Department of Health, Education, and Wel-          soliciting participation by prisoners in the
expulsion, a dead fetus, and isolated fetal        fare research, development, and demonstra-         research activity to determine that all ele-
tissue or organs excised from a dead fetus.        tion activities involving prisoners as subjects.   ments of informed consent, as outlined in
    (h) “Viability of a fetus” means capabil-         (b) The requirements of this subpart are        § 46.3, are satisfied; (2) overseeing the selec-
ity given the benefit of available therapy, of     in addition to those imposed under subparts        tion of prisoners who may participate in the
independently maintaining heart beat and           A and B of this part.                              activity; (3) monitoring the progress of the
respiration.                                          Section 46.42 Purpose. It is the purpose of     research and the continued willingness of
    (i) “In vitro fertilization” means any fer-    this subpart to provide additional safeguards      subject participation; and (4) intervening
tilization of human ova which occurs outside       for activities to which this subpart is appli-     on behalf of one or more subjects if condi-
the body of a female, through admixture of         cable inasmuch as the potential subjects in        tions warrant. In addition, each subject will
human sperm and such ova.                          activities conducted thereunder, because of        be informed of the name of a member of the
    Section 46.34 Duties of the Ethical Re-        their incarceration, might be under con-           Protection Committee who will be available
view board. (a) It shall be the function of        straints which could affect their ability to       to the subject for consultation concerning the
the Board to review each activity to which         make a truly voluntary and uncoerced de-           activity.
this subpart applies and advise the agency         cision whether or not to participate in such          (b) Each Protection Committee shall be
concerning the acceptability of such activi-       activities.                                        composed of at least five members appointed
ties from the standpoint of societal need and         Section 46.43 Definitions. As used in this      by the applicant and so selected that the
ethical considerations, taking into account        subpart:                                           Committee will be competent to deal with the
the assessment of the appropriate Primary             (a) “DHEW activity” means:                      medical, legal, social, and ethical issues in-
Review Committees as to: (1) The potential            (1)   the conduct or support (through           volved. At least one member of the Committee
benefit of the proposed activity, (2) scien-       grants, contracts, or other awards) of bio-        shall be either a prisoner or a representative
tific merit and experimental design, (3) the       medical or behavioral research involving           of an organization having as a primary con-
sufficiency of studies involving animals dem-      human subjects; or                                 cern protection of the interests of prisoners.

                                       FEDERAL REGISTER, VOL. 38, NO. 221—FRIDAY, NOVEMBER 16, 1973
31748                                                                NOTICES
No more than one-third of the members may          guards for the mentally infirm involved in         an Organizational Review Committee where
be physicians or scientists engaged in bio-        research, development, and demonstration           no such Committee has been established
medical or behavioral research, and no more        activities, inasmuch as the potential subjects     under subpart A.
than one member, other than a prisoners’           in such activities are: (1) Confined in an            Section    46.50   Protection  Committees;
representative, may have any affiliation with      institutional setting; (2) might be unable         duties; composition. (a) No activity covered
the prison facility or the legal entity having     fully to comprehend the type risks which           by this subpart will be approved unless it
jurisdiction over the facility, except for per-    may be involved; and (3) might be legally          provides for the establishment of a Protec-
sons employed by a Department of Education         incompetent to consent to        their particip-   tion Committee to carry out the following
in a teaching capacity. Any prisoners serving      tion in such activities.                           functions, as well as any others prescribed
on the Committee shall be compensated at a            Section 46.53 Definitions. As used in this      by the Organizational Review Committee or
rate consistent with that set for prisoners        subpart:                                           by DHEW: (1) Overseeing the process of
participating as subjects in activities at the        (a) “DHEW activity” means:                      selection of subjects who may be included
facility to which this subpart is applicable.         (1) The conduct or support (through             in the activity, (2) monitoring the progress
   (c) The Protection Committee shall estab-       grants, contracts, or other awards) of bio-        of the activity with special attention to
lish rules of procedure for conducting its         medical or behavioral research involving           adverse effects on subjects, (3) intervening
activities which must be reviewed by DHEW,         human subjects; or                                 on behalf of one or more of the subjects if
and shall conduct its activities at convened          (2) Research, development, or demonstra-        conditions warrant, (4) evaluating the proc-
meetings, minutes of which shall be prepared       tion activities regulated by any DHEW              ess and reasonableness of consent of the
and retained. The composition of the Com-          agency.                                            legal guardian and (where applicable) of the
mittee shall be subject to DHEW approval.             (b) “Mentally infirm” includes the men-         subject, and (6) advising the legal guardian
   Section 46.46     Prohibition on participa-     tally ill, the mentally retarded, the emotion-     and/or the subject concerning the latter’s
tion in activities prior to conviction. No in-     ally disturbed, the psychotic, the senile, and     continued participation in the activity if
dividual confined pending arraignment, trial,      others with impairments of a similar nature,       conditions warrant.
or sentencing for an offense punishable as a       regardless of whether or not the individual           (b) The composition of each Protection
crime may be used as a subject in any ac-          has     been      determined   to    be  legally   Committee shall conform to the require-
tivity supported in whole or in part by a          incompetent.                                       ments set forth in § 46.26 (a).
grant or contract to which this subpart is            (c)    “Institutionalized” means confined,         (c) The Protection Committee shall es-
applicable.                                        whether by court order or voluntary com-           tablish rules of procedure for conducting its
   Section 46.47 Remuneration to subjects.         mitment, in an institution for the care and/       activities, which must be reviewed by DHEW,
Where rates of remuneration are set pursu-         or treatment of the mentally infirm.               and shall conduct its activities at convened
ant to § 46.44 of this subpart, any subject           Section 46.54 Limitations on activities in-     meetings, minutes of which shall be prepared
who, for medical reasons, is required by a         volving the institutionalized mentally infirm.     and retained.
representative of the prison facility, grantee,    No institutionalized mentally infirm indi-            Section 46.57 Activities to be performed
contractor, or sponsor of the activity, to with-   vidual may be included as a subject in a           outside the United States. In addition to
draw before completion of his or her partici-      DHEW activity unless:                              satisfying all other applicable requirements
pation in the activity shall continue to be           (a) The proposed activity is concerned          in this subpart, an activity to which this
compensated for a period to be set by the          with: (1) The diagnosis, treatment, preven-        subpart is applicable, which is to be con-
Protection Committee after consultation with       tion, or etiology of the impairment with           ducted outside the united States, must in-
the grantee or contractor.                         which he or she is afflicted; or (2) the pro-      clude written documentation satisfactory to
                                                   posed activity is concerned with the effect        DHEW that the proposed activity is accept-
   Section 46.48 Accreditation. It is the in-
                                                   of institutional life on the subject and in-       able under the legal, social, and ethical
tention of DHEW to accredit, prison facilities
as sites for the performance of activities to      volves no risk of harm to the subject; or          standards of the locale in which it is to be
                                                   (3) the information can be obtained only           performed.
which this subpart applies. Accreditation
will be based on certification of the accepta-     from such subjects.
                                                      (b) The individual’s legal guardian has               SUBPART F—GENERAL PROVISIONS
bility of the facilities and compliance with
the procedures required by this subpart, as        given consent to the individual’s participa-          Section 46.61 Applicability. The following
determined by the Secretary. No activity           tion in such activity;                             regulations are applicable to all activities
covered by this subpart may involve prison-           (c) Where the individual has sufficient         covered by this part.
ers incarcerated in a facility not accredited      mental competency to understand what is
                                                   proposed and to express an opinion as to his          Section 46.62 Records. (a) Copies of all
by Secretary of DHEW.                                                                                 documents presented or required for initial
   Section 46.49 Activities to be performed        or her participation, the individual’s con-
                                                   sent to such participation has also been           and continuing review by any Organizational
outside the United States. In addition to                                                             Review Committee or Protection Committee
                                                   secured; and
satisfying all other applicable requirements                                                          and minutes, transmittals on actions, in-
in this subpart, an activity to which this sub-       (d) The Protection Committee, provided
                                                   for in § 46.50 of this subpart, has reviewed       structions, and conditions resulting from
part is applicable, which is to be conducted                                                          committee deliberations are to be made part
outside the United States, must include writ-      and approved subject participation in the
                                                   activity (by class or by individual).              of the official files of the grantee or con-
ten documentation satisfactory to DHEW                                                                tractor for the supported activity.
that the proposed activity is acceptable under         Section 46.55 Additional duties of Organ-
                                                   izational Review Committee where the men-             (b) Records of subject’s and representa-
the legal, social, and ethical standards of the                                                       tive’s consent shall be retained by the
locale in which it is to be performed.             tally infirm are involved. (a) In addition to
                                                   its responsibilities under Subpart A of this       grantee or contractor in accordance with its
SUBPART E—ADDITIONAL PROTECTIONS FOR IN-           part, the Organizational Review Committee          established practice, or, if no practice has
  STITUTIONALIZED MENTALLY INFIRM INDIVID-         shall, with respect to activities to which         been established, in project files.
  UALS INVOLVED AS SUBJECTS IN DHEW AC-            subpart applies:                                      (c) Acceptance of any DHEW grant or
                                                                                                      contract award shall constitute consent of
  TIVITIES                                            (1) Certify that all aspects of the activity    the grantee or contracting organization to
   Section 46.51 Applicability. (a) The regu-      would be ethically appropriate for perform-        inspection and audit of records pertaining to
lations in this subpart are applicable to all      ance on healthy individuals;                       the assisted activity by authorized repre-
Department of Health, Education, and Wel-             (2) Conduct at least one on-site visit to       sentatives of the Secretary.
fare activities involving the institutionalized    the institution and prepare a report of the           (d) All documents and other records re-
mentally infirm as subjects.                       visit including discussion of such matters         quired under this part must be retained by
   (b) Nothing in this subpart shall be con-       as living conditions, availability of medical      the grantee or contracting organization for
strued as indicating that compliance with the      care, and quality of food, to be submitted to      a minimum of three years following termina-
procedures set forth herein in connection          DHEW along with the application;                   tion of DHEW support of the activity.
with activities permitted under § 46.54 of this       (3) Review and approve or modify the               Section 46.63 Reports. Each organization
subpart will necessarily result in a legally       procedures proposed by the applicant to be         with an approved assurance shall provide the
effective consent under applicable State or        followed by the Protection Committee, pro-         Secretary with such reports and other in-
local law to a subject’s participation in such     vided for in § 46.56, in overseeing the re-        formation as the Secretary may from time to
an activity; nor in particular does it obviate     cruitment of the mentally infirm subjects          time prescribe.
the need for court approval of such participa-     who may be included in such activity;                 Section    46.64 Early     termination  of
tion where court approval is required under           (4) Recommend any additional functions          awards; sanctions for noncompliance. (a)
applicable State or local law in order to          to be performed by the Protection Commit-          If, in the judgment of the Secretary, an or-
obtain a legally effective consent.                tee in connection with any particular ac-          ganization has failed to comply with the
   (c) The requirements of this subpart are        tivity; and
                                                                                                      terms of this part with respect to a par-
in addition to those imposed under subparts           (5) Carry out such other responsibilities       ticular Federal activity, he may require that
A, B, and D of this part.                          as may be recommended by DHEW.                     said grant or contract be terminated or sus-
   Section 46.52 Purpose. It is the purpose           (b) Activities to which this subpart is ap-     pended in the manner prescribed in appli-
of this subpart to provide additional safe-        plicable must provide for the designation of       cable grant or procurement regulations.

                                     FEDERAL REGISTER, VOL. 38, NO. 221—FRIDAY, NOVEMBER 16, 1973
                                                                   NOTICES                                                                31749
   (b) If, in the judgment of the Secretary,         (c) If, in the judgment of the Secretary,      continue until it is shown to the satisfaction
an organization fails to discharge its re-        an individual serving as principal investi-       of the Secretary that the reasons therefor no
sponsibilities for the protection of the rights   gator, program director, or other person hav-     longer exist.
and welfare of the subjects in its care,          ing responsibility for the scientific and tech-     Section 46.65 Conditions. The Secretary
whether or not DHEW funds are involved, he        nical direction of a project or activity, has     may with respect to any activity or any class
may, upon reasonable notice to the organiza-      failed to discharge her or his responsibilities
tion of the basis for such action, determine                                                        of activities impose conditions, including
                                                  for the protection of the rights and welfare
that its eligibility to receive further DHEW      of human subjects in his or her care, the         conditions pertaining to informed consent,
grants or contracts or participate in DHEW        Secretary may, upon reasonable notice to the      prior to or at the time of the approval of
assisted activities, involving human subjects,    individual of the basis for such action, deter-   any activity when in the Secretary’s judg-
shall be terminated. Such disqualification        mine that such individual’s eligibility to        ment such conditions are necessary for the
shall continue until it is shown to the satis-    serve as a principal investigator or program      protection of human subjects.
faction of the Secretary that the reasons         director or in another similar capacity shall
therefor no longer exist.                         be terminated. Such disqualification shall         [FR DOC. 73–23922 Filed 11–15–73; 8:45 am]

                                    FEDERAL REGISTER, VOL. 38, NO. 221—FRIDAY, NOVEMBER 16, 1973

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